Nicotinic acetylcholine receptors (nAChRs) are essential to behaviors as basic as breathing and as mysterious as motivation, memory and mood. The overall goal of the NS 022061 program is elucidate the role of central cholinoceptive circuits that are affected in neuropsychiatric, neurodegenerative and addictive disorders, with the long range goal of accelerating the development of novel therapeutics. Whereas prior studies have been limited to probing the role of nicotinic acetylcholine receptors (nAChRs) in cholinoceptive circuits by application of agonists or antagonists, we are now armed with multiple genetic, optogenetic and new molecular tools that permit dissection of how direct activation of endogenous cholinergic neurons regulates cortico-limbic excitability. With these new approaches in hand, we can test how cortico-limbic circuits are altered by peri-natal vs. adolescent exposure to nicotine, the world's most common drug of abuse.

Public Health Relevance

Despite the crucial role of acetylcholine throughout life and the fact that nicotine self- administration is the single greatest cause of preventable death in the world, basic aspect of cholinergic signaling remain mysterious. The goal of this project is to determine how acetylcholine modulates cortico-limbic circuits that are pertinent to motivated behaviors, by modulating the activity of brain regions conveying information related to emotional context, sensory cues, executive function and novelty vs. prior experience.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01NS022061-30
Application #
8681541
Study Section
Molecular Neuropharmacology and Signaling Study Section (MNPS)
Program Officer
Stewart, Randall R
Project Start
Project End
Budget Start
Budget End
Support Year
30
Fiscal Year
2014
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Groessl, Florian; Jeong, Jae Hoon; Talmage, David A et al. (2013) Overnight fasting regulates inhibitory tone to cholinergic neurons of the dorsomedial nucleus of the hypothalamus. PLoS One 8:e60828
Mansvelder, Huibert D; Mertz, Marjolijn; Role, Lorna W (2009) Nicotinic modulation of synaptic transmission and plasticity in cortico-limbic circuits. Semin Cell Dev Biol 20:432-40
Jiang, Li; Role, Lorna W (2008) Facilitation of cortico-amygdala synapses by nicotine: activity-dependent modulation of glutamatergic transmission. J Neurophysiol 99:1988-99
Jo, Young-Hwan; Wiedl, Denise; Role, Lorna W (2005) Cholinergic modulation of appetite-related synapses in mouse lateral hypothalamic slice. J Neurosci 25:11133-44
Jo, Young-Hwan; Chen, Ying-Jiun J; Chua Jr, Streamson C et al. (2005) Integration of endocannabinoid and leptin signaling in an appetite-related neural circuit. Neuron 48:1055-66
Fischer, Harald; Orr-Urtreger, Avi; Role, Lorna W et al. (2005) Selective deletion of the alpha5 subunit differentially affects somatic-dendritic versus axonally targeted nicotinic ACh receptors in mouse. J Physiol 563:119-37
Bao, Jianxin; Lei, Debin; Du, Yafei et al. (2005) Requirement of nicotinic acetylcholine receptor subunit beta2 in the maintenance of spiral ganglion neurons during aging. J Neurosci 25:3041-5
Jo, Young-Hwan; Talmage, David A; Role, Lorna W (2002) Nicotinic receptor-mediated effects on appetite and food intake. J Neurobiol 53:618-32
Ibanez-Tallon, Ines; Miwa, Julie M; Wang, Hai Long et al. (2002) Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1. Neuron 33:893-903
Jo, Young-Hwan; Role, Lorna W (2002) Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. J Neurosci 22:4794-804

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